Hyperactivation is a dramatic change in the motility pattern of human and other mammalian sperm that occurs prior to fertilization in the female reproductive tract or in vitro. It is thought to assist the sperm in reaching the site of fertilization and penetrating the vestments of the egg. The long term goals of this project are to study the functions and control mechanisms for hyperactivation and to determine its relationship to sperm capacitation. At this point, the specific aims are to examine 1) how hyperactivation moves sperm through the female reproductive tract, by following the movement of individual mouse sperm through excised tracts; 2) the advantages of hyperactivation, by comparing the abilities of prehyperactivated and hyperactivated sperm to make progress through artificial environments that simulate physical aspects of the female tract; 3) the relationship of intracellular calcium levels to hyperactivated motility, by using the fluorescent calcium chelator Fura-2 in conjunction with computerized video analysis of fluorescence and flagellar bending patterns; 4) the relationship between calcium changes in the sperm head, which occur during capacitation, and hyperactivation, again using Fura-2. The mouse will be used as an animal model for the first aim because sperm may be observed through the walls of its uterus and oviduct; mouse and hamster sperm will be used for the second aim because their motility patterns encompass the range observed among mammalian sperm; and hamster sperm will be used for the last two aims because they are large enough to enable visual ascertainment of the state of the acrosome and image analysis of Fura-2 fluorescence. The information learned from these studies can be used to treat infertility as well as to develop new methods of contraception that work prior to fertilization.